Genetic studies in mental subnormality.

Date:
1973
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Genetic studies in mental subnormality. Source: Wellcome Collection.

    23/100 (page 9)
    PATTERNS OF DISTRIBUTION 9 there are three severely subnormal males living at home, the offspring of a woman by two different men, has been in the area for some years but was not ascertained during the survey, perhaps because this family has always been considered difficult and unco-operative, and it was wrongly assumed that its members would refuse to take part in the study. It seems to the author that there are a remarkable number of pedigrees of idiopathic mental defect which are compatible with X-linkage in the families ascertained in this study. As was pointed out in Chapter I, in the review of the literature, very few such pedigrees have previously been reported. All the twelve families noted above are at least as consistent as those few previously published where there was evidence for such a hypothesis. It is impossible not to be impressed by the number of these pedigrees and by one or two of them where any other explanation than X-linkage or sex limitation is difficult to con¬ ceive, in particular perhaps families Nos. 103, 108, 228 and 248, and AS/655. It would be hazardous to attempt any formal goodness of fit analysis with an X-linked hypothesis in respect of sibships which include affected males. In families where males only in one sibship are affected there must, by reason of the mode of ascertainment, be at least two affected males in each sibship. Even in families where cases occur in different sibships in the same or different generations, there must have been biases in ascertainment in favour of families where two or more cases occurred in the latest generation. As a matter of interest, Table IV sets out the data concerning affected and unaffected males in sibships in all-male affected families where there was or was not more than one sibship which included affected males. This is probably not very different from what would have been expected if all cases had been due to X-linked recessive genes. However, it seems unwise to try to derive an expectation on such a hypothesis in view of the impossibility of defining modes of ascertainment with confidence. Pedigrees of families where both males and females or only females were severely subnormal In all, there were 91 families where females only or both males and females were affected. It seems reasonable to assume that usually when two or more close relatives are severely subnormal the aetiology is the same in all those affected. If, this simplifying assumption is made, there may be four possible explanations of the occurrence of two or more cases in these 91 families. 1. The cause could be segregating autosomal recessive genes. It seems certain that there is an autosomal recessive contribution to these 'idio¬ pathic' cases, and that there are many loci at which such recessive genes occur. This leads to two expectations : unless close relatives of index cases had contracted consanguineous marriages, it would be exceptional for cases to occur in more than one sibship; and a significant proportion of affected sibs would have con¬ sanguineous parents. 2. Fully penetrant autosomal dominant genes could not be an explanation unless in the exceptional cases where severely subnormal girls have children. Males with this degree of defect seldom, if ever, reproduce. However, there may be dominant genes whose effects are subject to Table IV Distribution of idiopathic severe subnormality in families with only males affected